Seeding, maturation and propagation of amyloid beta-peptide aggregates in Alzheimer's disease

Li, TXiaohang; Ospitalieri, Simona; Robberechts, Tessa; Hofmann, Linda; Schmid, Christina; Upadhaya, Ajeet Rijal; Koper, Marta J.; Arnim, Christine A. F von.; Kumar, Sathish; Willem, Michael; Gnoth, Kathrin; Ramakers, Meine; Schymkowitz, Joost; Rousseau, Frederic; Walter, Jochen; Ronisz, Alicja; Balakrishnan, Karthikeyan und Thal, Dietmar Rudolf (2022): Seeding, maturation and propagation of amyloid beta-peptide aggregates in Alzheimer's disease. In: Brain, Bd. 145, Nr. 10: S. 3558-3570

Abstract

Alzheimer's disease is neuropathologically characterized by the deposition of the amyloid beta-peptide (A beta) as amyloid plaques. A beta plaque pathology starts in the neocortex before it propagates into further brain regions. Moreover, A beta aggregates undergo maturation indicated by the occurrence of post-translational modifications. Here, we show that propagation of A beta plaques is led by presumably non-modified A beta followed by A beta aggregate maturation. This sequence was seen neuropathologically in human brains and in amyloid precursor protein transgenic mice receiving intracerebral injections of human brain homogenates from cases varying in A beta phase, A beta load and A beta maturation stage. The speed of propagation after seeding in mice was best related to the A beta phase of the donor, the progression speed of maturation to the stage of A beta aggregate maturation. Thus, different forms of A beta can trigger propagation/maturation of A beta aggregates, which may explain the lack of success when therapeutically targeting only specific forms of A beta.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0006-8950
• Sprache: Englisch